Cancer reprograms immune cells to avoid an attack

Cause a specific type of white blood cell to change its identity.

Under normal conditions, immune cells mature along a rigidly circumscribed path. Myeloid progenitor cells in the bone marrow can become monocytes (white blood cells that engulf pathogens), or they can differentiate down a parallel path to become granulocytes (white blood cells that create pus). Once they commit to one or the other path, they don't seem to be able to switch fates.

But work recently reported in Nature Immunology suggests that cancerous cells can re-engineer these immune cells, causing them to do just that. And they are induced to do so by the misregulation of one of the most well-studied oncogenes there is: the retinoblastoma (Rb) gene.

The immune system is normally capable of responding to cancer. But immature myeloid cells that tone down the immune response accumulate in the presence of tumors. These suppressor cells can be either monocyte-like or granulocyte-like, and it had been thought that they come from cells that are already committed to one of the two paths.

The researchers took both cell types out of mice with cancer and grew them in a culture mimicking the cancer context. They found that the monocyte-like cells grew much faster and survived much better than the granulocyte-like cells—yet somehow, the cultures were consistently enriched in the granulocyte-like suppressive cells. The researchers conclude that the pool of granulocyte-like cells “may be replenished from” the better-growing monocyte-like cells.

The same was true in mice: when the monocyte-like cells from mice with cancer were transferred into normal mice, they remained true to their fates. When they were transferred into new mice with cancer, they turned into granulocyte-like cells.

How does cancer manage to get these cells to switch fates? The researchers looked at the retinoblastoma protein (pRb), a known tumor suppressor (mutations that disable or diminish pRb yield uncontrolled cell growth, and thus cancer). The researchers found that in both mice and humans with cancer, the monocyte-like suppressor cells—the ones that switch fates—have low levels of pRb.

To demonstrate that pRb regulates this aberrant change of fate, the researchers showed that mice that lack pRb have excessive numbers of the granulocyte-like suppressor cells. When pRb is inserted into the monocyte-like cells in mice with tumors (which normally have low levels of the protein), the proportion of granulocyte-like cells is decreased.

What's not understood yet is how cancer cells cause the difference in pRb levels. Clearly, it's advantageous for them to do so, since it tones down the immune response. But there has to be some sort of signaling network that allows them to do so. Identifying it could ultimately allow it to be blocked, which may rev up the immune response to cancer.

I have trouble believing that it is so easy to hijack the immune system and hence that it will be that easy to block the mechanism by which cancer can hijack it. If in all those million of years of evolution between the progenitors of rats and humans, the immune system is STILL so easily hijacked, I would have thought we would be extinct or have evolved a way to block this very scenario. I suspect that we will find that while this is one of the steps involved in the creation of cancer, this is not the only thing that happens and that we can't easily block the mechanism by which this hijacking of our immune system happens. Also, is cancer in this form, present in other non mammals?

EDIT: I say we would be extinct because pathogens would also evolve at some point that would also attack such a single point of failure. and there would come a time that one of those pathogens would be so virulent and deadly that we would all die before it evolved a way of just using us rather than killing us.

I have trouble believing that it is so easy to hijack the immune system and hence that it will be that easy to block the mechanism by which cancer can hijack it. If in all those million of years of evolution between the progenitors of rats and humans, the immune system is STILL so easily hijacked, I would have thought we would be extinct or have evolved a way to block this very scenario. I suspect that we will find that while this is one of the steps involved in the creation of cancer, this is not the only thing that happens and that we can't easily block the mechanism by which this hijacking of our immune system happens. Also, is cancer in this form, present in other non mammals?

EDIT: I say we would be extinct because pathogens would also evolve at some point that would also attack such a single point of failure. and there would come a time that one of those pathogens would be so virulent and deadly that we would all die before it evolved a way of just using us rather than killing us.

Cancer is a long term attack that (except for some varieties) rarely kills children. News flash: Evolution no longer cares about you once you reproduce. Therefore all you can say we are really engineered for by evolution is making more humans. I have often speculated that this is why it is so hard to change habits after adulthood. Whatever behaviors brought you through adolescence alive were successful as far as evolution is concerned.

Maybe there is something about this method of subverting the immune system that takes a long lead time to establish, and would not be useful in the quick attack scenario you lay out.

What's not understood yet is how cancer cells cause the difference in pRb levels. Clearly, it's advantageous for them to do so, since it tones down the immune response

Apologies if this is a stupid question, I have only a rudimentary understanding of biology.

It was my understanding that cancer is the result of uncontrolled cell replication. So Cancer is an error in cell replication, but cancer cells do not actively try and bypass the bodies immune system. Here it sounds like cancer cells are actively trying to bypass the immune system much like a pathogen would do.

I have trouble believing that it is so easy to hijack the immune system and hence that it will be that easy to block the mechanism by which cancer can hijack it. If in all those million of years of evolution between the progenitors of rats and humans, the immune system is STILL so easily hijacked, I would have thought we would be extinct or have evolved a way to block this very scenario. I suspect that we will find that while this is one of the steps involved in the creation of cancer, this is not the only thing that happens and that we can't easily block the mechanism by which this hijacking of our immune system happens. Also, is cancer in this form, present in other non mammals?

EDIT: I say we would be extinct because pathogens would also evolve at some point that would also attack such a single point of failure. and there would come a time that one of those pathogens would be so virulent and deadly that we would all die before it evolved a way of just using us rather than killing us.

I doubt all the effort that has gone in to cancer research to make this discovery possible and the subsequent effort to create a usable therapy from it could be classified as "easy" in the evolutionary sense.

What's not understood yet is how cancer cells cause the difference in pRb levels. Clearly, it's advantageous for them to do so, since it tones down the immune response

Apologies if this is a stupid question, I have only a rudimentary understanding of biology.

It was my understanding that cancer is the result of uncontrolled cell replication. So Cancer is an error in cell replication, but cancer cells do not actively try and bypass the bodies immune system. Here it sounds like cancer cells are actively trying to bypass the immune system much like a pathogen would do.

The way I think about it is that cancer starts with an error in cell replication. That by itself isn't usually a problem because the body has ways to take out the trash. You don't start to have a problem until the garbage men go on strike.

My take away from this article is that researches might have found one reason the garbage men might be on strike - low levels of pRB. Now they need to find out what is causing the low levels so they can stop it, or find a way to raise levels again.

As with a real sanitation strike though, I'm sure the problem is more complex with many problems to be solved.

What's not understood yet is how cancer cells cause the difference in pRb levels. Clearly, it's advantageous for them to do so, since it tones down the immune response

Apologies if this is a stupid question, I have only a rudimentary understanding of biology.

It was my understanding that cancer is the result of uncontrolled cell replication. So Cancer is an error in cell replication, but cancer cells do not actively try and bypass the bodies immune system. Here it sounds like cancer cells are actively trying to bypass the immune system much like a pathogen would do.

I agree, I do not claim to be an expert in the field either, but this does make it seem like cancer could potentially have some of the properties of an auto-immune disease, such as AIDS or Lupus. If this is the case, it would be interesting to see what forms of therapy could be applied from the field of study for auto-immune diseases into the field of cancer/carcinogenic studies.

This could be a breakthrough in regards to cancer's ability to circumvent treatment that is currently available.

Cancer isn't a single disease. It's a thousand diseases, and every one of those is a facet of us being multicellular organisms that rely upon synergism rather than selfishness at a cellular level. "Identifying it could ultimately allow it to be blocked, which may rev up the immune response to cancer" is a bit of a broad statement. It might rev up the response to that specific cancer. But not "cancer" in the generic sense.

What's not understood yet is how cancer cells cause the difference in pRb levels. Clearly, it's advantageous for them to do so, since it tones down the immune response

Apologies if this is a stupid question, I have only a rudimentary understanding of biology.

It was my understanding that cancer is the result of uncontrolled cell replication. So Cancer is an error in cell replication, but cancer cells do not actively try and bypass the bodies immune system. Here it sounds like cancer cells are actively trying to bypass the immune system much like a pathogen would do.

I agree, I do not claim to be an expert in the field either, but this does make it seem like cancer could potentially have some of the properties of an auto-immune disease, such as AIDS or Lupus. If this is the case, it would be interesting to see what forms of therapy could be applied from the field of study for auto-immune diseases into the field of cancer/carcinogenic studies.

This could be a breakthrough in regards to cancer's ability to circumvent treatment that is currently available.

This brings up a question I've pondered before: If cancer hijacks the immune system to hide itself, what happens when a pathogen infects a tumor? Would the cancer effectively hide the pathogen from the immune system as well?

From time to time people bring up how cancer incidence is lower in less developed societies, and I usually argue that when the children are dying from cholera and such they simply aren't living long enough to get cancer.

Now I'm wondering if the lower incidence is also caused in part by cancer hiding itself from the immune system a little too effectively, and being wiped out by pathogens that the immune system also doesn't see.

(Still, I wouldn't inject myself with flesh-eating bacteria if I thought I had a tumor, but I'd be surprised if no one in the field has had similar thoughts)

What's not understood yet is how cancer cells cause the difference in pRb levels. Clearly, it's advantageous for them to do so, since it tones down the immune response

Apologies if this is a stupid question, I have only a rudimentary understanding of biology.

It was my understanding that cancer is the result of uncontrolled cell replication. So Cancer is an error in cell replication, but cancer cells do not actively try and bypass the bodies immune system. Here it sounds like cancer cells are actively trying to bypass the immune system much like a pathogen would do.

pRb is actually a tumor suppressor protein. It regulates the switch from the G1 to the S phase in mitosis. It does so, by binding the E2F transcription factor as well as an HDAC (histon deacetylase). Itself is regulated by the CDK4/Cyclin D complex which phosphorylates pRb, which then releases E2F and HDAC.

It was first discovered in a tumor called Retinoblastoma, which had a mutated form of the tumorsuppressorgen and thusly did not correctly bind E2F and HDAC, which leads to an uncontrolled mitosis, thus letting tumors grow uncontrolled.

I actually think that E2F might lead to the transcription and translation of some sort of ligand in those tumor cells, which in turn binds to an (usual unused) receptor on the monocytes, which leads them to switch into granulocytes. It is thus not really "evading" the immune system but just uses an happy coincidence. Of course that's just a guess.

By the way people with leukemia can also get AIDS. Since HIV infects a certain subset of T-Cells (I believe CD4+ T-Cells). Leukemia can have a effect on different subsets of leukocytes. In fact I believe the "Berlin patient" was in fact "cured" from AIDS by receiving a bone marrow transplant from a HIV resistant donor after he also suffered from leukemia.

One more thing: many viruses actually hide from the immun system. The Ebstein Barr virus does so by infecting B-Cells and tuning its own protein production down. Those foreign proteins are what the immune system detects.

I have trouble believing that it is so easy to hijack the immune system and hence that it will be that easy to block the mechanism by which cancer can hijack it. If in all those million of years of evolution between the progenitors of rats and humans, the immune system is STILL so easily hijacked, I would have thought we would be extinct or have evolved a way to block this very scenario. I suspect that we will find that while this is one of the steps involved in the creation of cancer, this is not the only thing that happens and that we can't easily block the mechanism by which this hijacking of our immune system happens. Also, is cancer in this form, present in other non mammals?

EDIT: I say we would be extinct because pathogens would also evolve at some point that would also attack such a single point of failure. and there would come a time that one of those pathogens would be so virulent and deadly that we would all die before it evolved a way of just using us rather than killing us.

You forget that cancer cells are basically somatic cells. In immunological circles, it has been known that cancer microenvironment is important for years, this is largely immune-suppressive. Also, even when a immune response is elicited against a tumour T-cells can become "fatigued" which is a normal limiting mechanism to prevent autoimmunity and self-destructive, excessive responses to pathogens. The immune system doesn't do "friend or foe" there is a complex interplay of stimulatory and inhibitory responses and even more complexity involved in deciding the type of threat and therefore which mechanisms to use against it. And yes viruses can and do exploit it. Do you have cytomegalovirus? You probably do and you will have it for the rest of your life since like many other herpes viruses HSV, EBV, VZV it damps down your immune response to it. Your immune system's job is to keep you alive not keep you as some kind of "pure" specimen so its often better to call a truce than suffer too much collateral damage.

A "cancer" needs to pass many hurdles (e.g. there are many checkpoints in the cell itself) the immune system is just one of them and it has years to evolve ways to do it. Also, you never hear about all the times your immune system wiped out a pre-malignant mass. How many times do HPV transformed warts just shrivel and fall off people? Do you ever see badly written science reports in the popular press about that?

EDIT: I say we would be extinct because pathogens would also evolve at some point that would also attack such a single point of failure. and there would come a time that one of those pathogens would be so virulent and deadly that we would all die before it evolved a way of just using us rather than killing us.

I believe that pathogens are subject to evolutionary pressures that limit their virulence. If a pathogen ever evolves that is so successfully deadly that it kills its hosts instantly, it will probably kill everyone in range of infection and then promptly go extinct, or at least dormant. Since most pathogens rely in some fashion on their hosts' biochemistry for optimal reproductive success, the most widespread and evolutionarily successful pathogens are the ones that are either non-lethal or at least that spread much faster than they kill.

It's unlikely that a universally-lethal highly-infectious pathogen would arise at any given time, because the overall evolutionary pressure on diseases is actually away from being lethal. Less infectious lethal pathogens kill their vectors and don't reach the full vulnerable population. It can happen, which is why we've had pandemics in human history.

Lastly, just disabling the immune system isn't a free pass. After all, most plants and simpler organisms don't have anything like the human immune system, but they still find enough ways to resist or avoid disease enough to get by. Something tells me that many of the factors that apply in those cases also work in our favor, above and beyond the benefits we get from our immune systems and from being smart enough to fight back on time scales of years rather than generations.

This brings up a question I've pondered before: If cancer hijacks the immune system to hide itself, what happens when a pathogen infects a tumor? Would the cancer effectively hide the pathogen from the immune system as well?

From time to time people bring up how cancer incidence is lower in less developed societies, and I usually argue that when the children are dying from cholera and such they simply aren't living long enough to get cancer.

Now I'm wondering if the lower incidence is also caused in part by cancer hiding itself from the immune system a little too effectively, and being wiped out by pathogens that the immune system also doesn't see.

(Still, I wouldn't inject myself with flesh-eating bacteria if I thought I had a tumor, but I'd be surprised if no one in the field has had similar thoughts)

You can inject anaerobic bacteria since the tumour is usually oxygen starved, and they will eat it from the inside out! But the immune system CAN see the tumour the problem is that it sees it as well mostly you but that's because it is.

As for less developed countries: most adult tumours take 20+ years to get from one aberrant cell to nasty mets in your lungs etc so if you don't make it much past 20... Also smoking, binge drinking, obesity have all be shown to be risk factors, risk factors that starving people tend to score quite well on.

Lastly, just disabling the immune system isn't a free pass. After all, most plants and simpler organisms don't have anything like the human immune system, but they still find enough ways to resist or avoid disease enough to get by. Something tells me that many of the factors that apply in those cases also work in our favor, above and beyond the benefits we get from our immune systems and from being smart enough to fight back on time scales of years rather than generations.

Yes, there is good evidence that virulence factors and immune escape mechanisms place a not insignificant genetic burden on the pathogen. e.g. HIV looses the genetic adaptions it acquires in people who possess protective HLA molecules (the so called long term suppressors) the moment it is passed onto a more susceptible individual clearly indicating those adaptions have a negative effect on overall viral fitness.

I have trouble believing that it is so easy to hijack the immune system and hence that it will be that easy to block the mechanism by which cancer can hijack it. If in all those million of years of evolution between the progenitors of rats and humans, the immune system is STILL so easily hijacked, I would have thought we would be extinct or have evolved a way to block this very scenario. I suspect that we will find that while this is one of the steps involved in the creation of cancer, this is not the only thing that happens and that we can't easily block the mechanism by which this hijacking of our immune system happens. Also, is cancer in this form, present in other non mammals?

EDIT: I say we would be extinct because pathogens would also evolve at some point that would also attack such a single point of failure. and there would come a time that one of those pathogens would be so virulent and deadly that we would all die before it evolved a way of just using us rather than killing us.

Without exception, cancer cells cannot generally exhibit behaviour that is not already present within the body in a controlled fashion. The ability to metastasize, cause angiogenesis, survive in multiple parts of the body, undergo mitosis - these are all necessary capabilities for the body to function normally. As tumours expand, they may have tens of billions of cells and - through relatively high rates of mutation - they will often chance upon certain mutations or open certain pathways that allow them to progress. That it doesn't occur more often than it does is actually a sign of the strength of our immune systems.

Just like the abilities described above, forcing or encouraging immune cells to change form is probably a necessary function in certain cells. I am guessing here, but perhaps sperm need that sort of thing to prevent being exterminated? Alternatively, maybe it is used by essential bacteria or cells in the digestive system to protect the bacteria that allow us to survive?

What's not understood yet is how cancer cells cause the difference in pRb levels. Clearly, it's advantageous for them to do so, since it tones down the immune response

Apologies if this is a stupid question, I have only a rudimentary understanding of biology.

It was my understanding that cancer is the result of uncontrolled cell replication. So Cancer is an error in cell replication, but cancer cells do not actively try and bypass the bodies immune system. Here it sounds like cancer cells are actively trying to bypass the immune system much like a pathogen would do.

The way I think about it is that cancer starts with an error in cell replication. That by itself isn't usually a problem because the body has ways to take out the trash. You don't start to have a problem until the garbage men go on strike.

My take away from this article is that researches might have found one reason the garbage men might be on strike - low levels of pRB. Now they need to find out what is causing the low levels so they can stop it, or find a way to raise levels again.

As with a real sanitation strike though, I'm sure the problem is more complex with many problems to be solved.

Remember that cancer really describes many different diseases, given the vastly different profiles of different cell tumours. AIDS can be associated with certain cancers, as its suppression of the immune system allows the cancer to take hold. Kaposi sarcoma is an example of one of these.

Still, as far as I understand it, AIDS mainly compromises the immune system by destroying T cells. I wouldn't be surprised if T cells play a critical role in the prevention of Karposi sarcoma, but a lesser role in the prevention of tumours in cells of other types, which may explain why only certain cancers seem to run rampant in those with AIDS. Of course, it may also be due to the fact that full blown AIDS sufferers are unlikely to survive long enough for many tumours to progress to the point where they are life threatening; pancreatic adenocarcinoma may be 20 years old when it causes symptoms.

Cancer isn't a single disease. It's a thousand diseases, and every one of those is a facet of us being multicellular organisms that rely upon synergism rather than selfishness at a cellular level. "Identifying it could ultimately allow it to be blocked, which may rev up the immune response to cancer" is a bit of a broad statement. It might rev up the response to that specific cancer. But not "cancer" in the generic sense.

Blocking it may also need to done in a controlled fashion; the ability to evade the immune system may serve a vital function in certain cells.

Somewhat off-topic, I wonder if you could get AIDS if you have leukemia?

Cancers of the T cells - the primary target of HIV - are only a subset of leukemia, which covers cancers of most blood cell types (not just T cells). I have no idea if mutations in T cells in those with T cell leukemia prevent HIV infection. It might be a point of interest if experimentation could be devised to test it - do T cells in those with T cell cancer develop mutations to resist HIV (or at least some of them)?

This brings up a question I've pondered before: If cancer hijacks the immune system to hide itself, what happens when a pathogen infects a tumor? Would the cancer effectively hide the pathogen from the immune system as well?

From time to time people bring up how cancer incidence is lower in less developed societies, and I usually argue that when the children are dying from cholera and such they simply aren't living long enough to get cancer.

Now I'm wondering if the lower incidence is also caused in part by cancer hiding itself from the immune system a little too effectively, and being wiped out by pathogens that the immune system also doesn't see.

(Still, I wouldn't inject myself with flesh-eating bacteria if I thought I had a tumor, but I'd be surprised if no one in the field has had similar thoughts)

There is an entire school of thought on the use of pathogens to trigger immune response to destroy tumours, and in many cases it has been experimentally shown to be quite effective. Heck, there are proper pharmaceuticals that work on the principle - Aldara (imiquimod) is a skin cream that is designed to trigger immune response to destroy certain skin cancers, warts (basically benign tumours) and other similar skin conditions.

Somewhat off-topic, I wonder if you could get AIDS if you have leukemia?

Cancers of the T cells - the primary target of HIV - are only a subset of leukemia, which covers cancers of most blood cell types (not just T cells). I have no idea if mutations in T cells in those with T cell leukemia prevent HIV infection. It might be a point of interest if experimentation could be devised to test it - do T cells in those with T cell cancer develop mutations to resist HIV (or at least some of them)?

I never been on any meds and I'm very healthy. I'm still confuse on why I can't get AIDS or even transfer it( my gf and I have not use rubbers for 2 years and she is neg) I want to talk more about to to others but my English is not great and I have no idea where to start. 13 years of HIV with no meds is getting to me. If anyone want to know about me I be glad to answer any questions.

What's not understood yet is how cancer cells cause the difference in pRb levels. Clearly, it's advantageous for them to do so, since it tones down the immune response

Apologies if this is a stupid question, I have only a rudimentary understanding of biology.

It was my understanding that cancer is the result of uncontrolled cell replication. So Cancer is an error in cell replication, but cancer cells do not actively try and bypass the bodies immune system. Here it sounds like cancer cells are actively trying to bypass the immune system much like a pathogen would do.

A lot of cancers are immunosuppressive, or immunoresistant. The immune system has to have mechanisms to calm it down, or we would all die rather dramatically and early on from an immune response which got wildly out of control. In a tumor, the real Darwinian struggle is usually between genetically different clones of the tumor, and the stochastic nature of tumorigenic mutations means that any tumor cell has potential access to any part of the genome. A clone which picks up the ability to use immunosuppressive genes can now evade the immune system, giving it a large advantage over other clones which are facing a more vigorous immune attack. Some immune cell killing is done by direct toxic assault on cells; this is especially true for attacking pathogens. For cancers, the most likely way to be initially attacked by immune cells is for the immune cells to order the tumor cell to kill itself. And all cells contain a self-destruct sequence worthy of the starship Enterprise, which certain immune cells can activate. However, the self-destruct sequence is also supposed to be automatically triggered when the cell screws up its DNA replication more than a trivial amount. So early mutations in tumorigenesis are often in the self-destruct mechanism, ensuring it does not work by both the internal and the external triggering mechanisms, at which point the tumor becomes more of a job for the lower finesse, higher brutality, portions of the immune system. Ironically, but logically, some of the nastier actors in the immune system are among the most vulnerable to being ordered to "apoptose" (commit suicide), as we definitely do not want them hanging around and then doing stuff, where they do not belong. Turning off the heavies of the immune system locally is a great benefit to the lucky tumor, which can mutate to turn on the appropriate pathways. To the patient, not so much.

What's not understood yet is how cancer cells cause the difference in pRb levels. Clearly, it's advantageous for them to do so, since it tones down the immune response

Apologies if this is a stupid question, I have only a rudimentary understanding of biology.

It was my understanding that cancer is the result of uncontrolled cell replication. So Cancer is an error in cell replication, but cancer cells do not actively try and bypass the bodies immune system. Here it sounds like cancer cells are actively trying to bypass the immune system much like a pathogen would do.

Cancer cells don't need to bypass the system at first, they are already in there. They will however, be attacked by the immune system when they begin to replicate. Cancer immunology is a growing field, but as an idea of the areas size, a search on pubmed for "cancer immunology" returns over 220,000 hits.

I have trouble believing that it is so easy to hijack the immune system and hence that it will be that easy to block the mechanism by which cancer can hijack it. If in all those million of years of evolution between the progenitors of rats and humans, the immune system is STILL so easily hijacked, I would have thought we would be extinct or have evolved a way to block this very scenario. I suspect that we will find that while this is one of the steps involved in the creation of cancer, this is not the only thing that happens and that we can't easily block the mechanism by which this hijacking of our immune system happens. Also, is cancer in this form, present in other non mammals?

EDIT: I say we would be extinct because pathogens would also evolve at some point that would also attack such a single point of failure. and there would come a time that one of those pathogens would be so virulent and deadly that we would all die before it evolved a way of just using us rather than killing us.

Um. AIDS and HIV does this exact thing. It not only attacks the immune system direcdtly but also tells it that the virus cells are supposed to be there - sothe immune system doesn't know any better. (yeah that's a very kindergarten breakdown of it - but still)

In conditions such as Multiple Sclerosis (and other similar diseases) - something triggers the immune system to attack some portion of the body that in other people is a neceassary body mechanism. (in the case of MS this is the membrane between the brain and the skull. I don;t remember what this membrane is specifically for (without looking it up again) but it's supposed to be there

There are all sorts of triggers that causes the immune system to be highjacked and to do stuff it's not supposed to do.

Unfortunately no one knows what the triggers are and how to counter it yet.

Somewhat off-topic, I wonder if you could get AIDS if you have leukemia?

Cancers of the T cells - the primary target of HIV - are only a subset of leukemia, which covers cancers of most blood cell types (not just T cells). I have no idea if mutations in T cells in those with T cell leukemia prevent HIV infection. It might be a point of interest if experimentation could be devised to test it - do T cells in those with T cell cancer develop mutations to resist HIV (or at least some of them)?

I never been on any meds and I'm very healthy. I'm still confuse on why I can't get AIDS or even transfer it( my gf and I have not use rubbers for 2 years and she is neg) I want to talk more about to to others but my English is not great and I have no idea where to start. 13 years of HIV with no meds is getting to me. If anyone want to know about me I be glad to answer any questions.

Ok...there are a lot of things we don't yet understand about HIV. But I do hope that your GF knows that you are positive and that there is still a chance that you might infect her. For some reason you just have an extemely low virus count. That doesn't mean you don't have the virus, nor that you can't transmit it. It is just more unlikely to happen. I'm not sure about the US but at least here in Germany you can be sued for having unprotective sex when you know that you are positive, because you are actively endangering another person.